Life Threatening Dermatosesand Emergency In DermatologyAbraham Arimuko

Departemen Kulit dan KelaminRSPAD Gatot Soebroto Jakarta

Emergency situations can occur even in the doctors office.

An emergency can be reviewed for dermato- logic conditions: questioning, looking for signs of severity, examining mucous membranes are important.

Recognize these situations at their beginning in order to undertake appropriate emergency procedure.

Dermatologic casesCutaneous Adverse Drug ReactionDrug Eruption with Eosinophilia and Systemic Syndrome (DRESS)AngioedemaAnaphylactic Shock Staphylococcal Scalded Skin Syndrome (SSSS)Purpura Fulminans

Toxic epidermal necrotizing (T.E.N.) and StevensJohnson syndrome (SJS)

Severe, drug-induced skin reactions with a high morbidity and mortality.TEN-SJS : different severity levels of this disease. The difference is based on the evaluation of involved body surface ( BSA).The mortality is about 30% for TEN. Drugs are nearly always involved, but in about 20% of the cases they are not identified

Drugs high risk induce : allopurinol, sulfonamides, carbamazapine, lamotrigine, nevirapine, oxicam-NSAIDs, phenobarbital, and phenytoin.the prognosis of the patient : supportive management is most Treatments : corticosteroids, antihistamine, immunoglobulin, etc.

Classification of the consensus ( Bastuji-Garin et al.)

Clinical finding :Beginning signs = difficult to recognize : isolated fever, sore throat, cough or burning eyes.

The cutaneous eruption : erythematous macules, dark purpuric centres ( target lesion) : +/-

Within 13 days, flaccid blisters, sheet-like epidermal detachment appear, with Nikolskys sign. Mucous membrane erosions

The signs :

A rash accompanied by mucous involvement.MouthGenitalConjuntivaTenderness of the skin with burn sensation.Adenomegaly.High fever above 38.5C.

Erythema Exsudativum Multiforme Majus (EEMM), Typical targets lesions on palms

Confluent purpuric macules and fl at atypical targets in SJS

Early lesions of toxic epidermal necrolysis

Detachment of large epidermal sheets in TEN with maculae; atypical target lesions are still present

Therapeutic Concepts

Early DiagnosisManagement in the Emergency RoomTopical Treatment and Supportive CareImmuno-Modulating Treatment

DrugEruptionwithEosinophilia and Systemic Symptoms (DRESS)This cutaneous ADR is also severe, with mortality about 10%. The delay often very long up to 8 weeks.Organs can be involved: liver, kidney, myocardium, lung, and central nervous system.The culprit drugs : carbamazepine, allopurinol, hydantoin, lamotrigin, sulfonamides, minocycline, non-steroidal anti-inflammatory drugs, nevirapine, calcic inhibitors, methyldopa, terbinafin, neuroleptics, and dapsone.

Clinical :Lichenoid type erythrodermia Fever of more than 38.5C, Poor general condition Adenomegaly, in at least two localisationsPeri-orbital oedema Non-mucous involvementDrugs known to be inductors Very long delay between introduction of the drug and beginning of the ADR

AngioedemaType of urticaria, tender and thick tumefaction of the skin, no pruritus, it can be painful. Lips, cheeks, peri-orbital areas and tongue are often involved. Dysphonia, hyper-salivation, dysphagia, : involvement of the pharyngeal, risk of glottis oedema.

Anaphylactic ShockThis occurs very quickly, usually less than 1 hour after introduction of the allergen. It is very important to recognize it quickly because of its gravity. Diffuse erythema with palmo-plantar pruritus, urticarial wheals, flush and dizziness are associated. Mucous oedema frequently involves nose, eyes, mouth, lips and tongue. Gastroenteric signs can induce in error:. Breathing becomes difficult because of oedema and bronchospasm. Laryngal cough or asthma can occur.Decrease of arterial pressure by intense vasodilata- tion is accompanied by tachycardia. Mental confusion or seizure may be consequences of hypoxemia. Dizziness and intense anxiety are always present.This is a true emergency; one should phone the emergency mobile unit. While awaiting their arrival, the patient must be placed in a supine position, oxygen (1015 l min1) should be administered, and epineph- rin injected intramuscularly in deltoid region or in the anterior face of the thigh. Average dosage in an adult is 0.5mg, in a child 0.01mg kg1. In absence of good evolution, another injection can be administered 510min after. In the case of bronchospasm, inhala- tion of salbutamol should be administered.Blood pressure, cardiac rate, ventilation and con- sciousness must be supervised. Intravenous infusion could be installed in order to perfuse macromolecules.The patient must always be hospitalized, even if the status is good, because of the risk of rapid recurrence.

Anaphylactic shock:Signs that should alert :Distal pruritic oedema and mucous involvementFlush phenomenon Respiratory : bronchospasmDigestive symptoms : abdominal pain, nausea and dysphagia Dizziness and anxiety Low blood pressure and tachycardia

StaphylococcalScaldedSkin Syndrome (SSSS)Blistering, exfoliative dermatosis, caused by the secretion of exotoxin from Staphylococcus aureus More frequently among children. The risk of death is about 5% in children.Erythematous rash, sub-corneal blistering Nikolskys sign is present. The fluid in blisters is usually sterile.

Purpura Fulminans:Observed with meningococcal infection Young children Begin with palpable purpura. larger than 3mm in diameter. Some of them may become necrotic.Fever, chills, hypotension, meningo-encephalitis, etc.Treatment : Antibiotic

Purpura fulminans

The pathophysiology of disseminated intravascular coagulation in bacterial infection-related purpura fulminans. Abbreviations: GAG, Glycosaminoglycans; aPC, activated protein C; PS, protein S; tPA, tissue plasminogen activator; TM, thrombomodulin; ADP, adenosine diphosphate; TAFI, thrombinactivated fi brinolysis inhibitor; PAI, plasminogen activator inhibitor-1; TF, tissue factor; TFPI, tissue factor pathway inhibitor; ATIII, antithrombin 3; PC, protein C; EPCR, endothelialprotein C receptor; Roman numerals, clotting factor; n, neutrophil; m: macrophage

MeningococcemiaHaemorrhagic lesions : universal distribution Diameter haemorrhages greater than 2 mmPoor overall condition Nuchal rigidity

two of the above criteria are present

Conclusion:Emergencies in the doctors office are uncommon, but their severity requires that the physician pays attention to the signs.

The need for equipment to respond to every life- threatening situation depends on the size of the practice, on the number of patients coming to the location, and on the proximity of the emergency service.

Toxic epidermal necrotizing (T.E.N.) or Lyells syndromeand StevensJohnson syndrome [1]: Toxic epidermalnecrotizing (TEN) and StevensJohnsonsyndrome (SJS) represent different severity levels ofthis disease. The difference is based on the evaluationof involved body surface area (BSA). They are the moresevere of the cutaneous adverse drug reactions (ADR).The mortality is about 30% for TEN. Drugs are nearlyalways involved, but in about 20% of the cases they arenot identifi ed despite very meticulous questioning.Beginning signs are often very diffi cult to recognize,but they are very important because it is known that themore rapid the clearance of the responsible drug, thebetter the prognosis [2]. The condition may begin byisolated fever, sore throat, cough or burning eyes. Thecutaneous eruption may be erythematous macules,sometimes with darker purpuric centres that tend tomerge. Usually, within 13 days, fl accid blisters and asheet-like epidermal detachment appear, with Nikolskyssign. Mucous membrane erosions are present, and thediagnosis is no longer diffi cult (Figs. 17.117.5).The signs that should alert the physician are:A rash accompanied by one mucous involv ement,even as minimal as a discrete conjunctivitis. Bifocal or multifocal involvement is highly suggestiveof a severe form of cutaneous ADR. Adenomegaly. High fever above 38.5C. Very high tenderness of the skin with burn sensation.

*This cutaneous ADR is also severe, with mortality about 10%. The delay before onset is often very long between the introduction of the causative drug and the first signs up to 8 weeks.Clinical signs are dominated by a very poor general condition, with high fever, important adenomegaly and the presence of erythematous macules quickly becom- ing a pruritic erythrodermia. The condition starts in the face and the upper trunk and then diffuses to the limbs. Peri-orbital oedema is quite impressive. Even if the vital prognosis is not immediately made, it is very important for the patient to be rapidly referred to a spe- cialized dermatologic unit. Biological perturbations will be associated, such as major hyper-eosinophilia, hyper-basophile lymphocytes, hepatic cytolysis and cholestasis, and renal impairment. All solid organs can be involved, such as liver, kidney, myocardium, lung, and central nervous system.The culprit drugs are mainly carbamazepine, allopurinol, hydantoin, lamotrigin, sulfonamides, minocycline, non-steroidal anti-inflammatory drugs, nevirapine, calcic inhibitors, methyldopa, terbinafin, neuroleptics, and dapsone.*This is an immediate-type hypersensitivity reaction. It corresponds to a profound type of urticaria. Skin localisation is possible but the danger comes from mucous involvement. Unlike the usual urticaria, angioedema is a tender and thick tumefaction of the skin. There is no pruritus; it can be painful. Lips, cheeks, peri-orbital areas and tongue are often involved. Occurrence of dysphonia, hyper-salivation, dysphagia, and signs of involvement of the pharyn- geal area must be considered as alert signs because of the risk of glottis oedema. Furthermore, appari- tion of an angioedema may precede anaphylactic shock. The best approach is to phone the emergency ambulance services; in the absence of signs of grav- ity such as dysphonia or hyper-salivation, corticos- teroids should be injected. Anti-histaminic drugs may be injected afterwards.In the case of signs of gravity or evolution towards an anaphylactic shock, epinephrine IM must be used. Dosage will be increased from 0.30 to 0.50 mg. It can be repeated every 1015min if necessary. An oxygen mask at 1015l min1 should be fitted while waiting the emergency mobile unit.*This occurs very quickly, usually less than 1 hour after introduction of the allergen. It is very important to recognize it quickly because of its gravity. Diffuse erythema with palmo-plantar pruritus, urticarial wheals, flush and dizziness are associated. Mucous oedema frequently involves nose, eyes, mouth, lips and tongue. Gastroenteric signs can induce in error: abdominal pain, especially epigastralgias, nausea and dysphagia. Breathing becomes difficult because of oedema and bronchospasm. Laryngal cough or asthma can occur.Decrease of arterial pressure by intense vasodilata- tion is accompanied by tachycardia. Mental confusion or seizure may be consequences of hypoxemia. Dizziness and intense anxiety are always present.This is a true emergency; one should phone the emergency mobile unit. While awaiting their arrival, the patient must be placed in a supine position, oxygen (1015 l min1) should be administered, and epineph- rin injected intramuscularly in deltoid region or in the anterior face of the thigh. Average dosage in an adult is 0.5mg, in a child 0.01mg kg1. In absence of good evolution, another injection can be administered 510min after. In the case of bronchospasm, inhala- tion of salbutamol should be administered.Blood pressure, cardiac rate, ventilation and con- sciousness must be supervised. Intravenous infusion could be installed in order to perfuse macromolecules.The patient must always be hospitalized, even if the status is good, because of the risk of rapid recurrence.

*This is a blistering, exfoliative dermatosis, caused by the secretion of exotoxin from Staphylococcus aureus [7].It occurs more frequently among children than adults. The risk of death is about 5% in children. It begins like an erythematous rash, with sub-corneal, blistering. It often begins in the flexures. Nikolskys sign is present. The fever is high and the child is exhausted. The fluid in blisters is usually sterile.The child must be quickly referred to a specialized unit where a bacterial research will be undertaken. The infecting strain is usually recovered from distant sites. The adapted antibiotic treatment is followed by a dra- matic efficacy.*Purpura fulminans is most frequently observed with meningococcal infection; however, it can also occur with other bacteria including groups A and B beta- haemolytic streptococci, S. pneumoniae, H. influen- zae... It occurs more frequently in young children than in adults, and can correspond to the first manifestations of meningococcemia.It may begin with palpable purpura. Elements are larger than 3mm in diameter. Some of them may become necrotic; necrosis first involves the extremi- ties. In addition to skin lesions, fever, chills, hypoten- sion, meningo-encephalitis, etc. may be observed. It is very important to perform this diagnosis, because the prognosis depends on the rapidity of starting the treatment. The first act to be performed is an intrave- nous or, if not possible, intramuscular injection of ceftriaxone (70100mg kg1 per day, reconstituted with steril water). This injection will improve theprognosis without compromising the later search for bacteria in the hemocult or in the spinal fluid. Every physician should have ceftriaxone in his office.

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